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The reactions of selected alpha,beta-unsaturated steroidal ketones with Lawesson's reagent (LR) in CH(2)Cl(2) and toluene under the standard reaction conditions and with a combination of phosphorus pentasulfide with hexamethyldisiloxane (P(4)S(10)/HMDO) in 1,2-dichlorobenzene (ODCB) under microwave irradiation were investigated and for this purpose several cholestane, androstane and pregnane carbonyl derivatives were chosen. Depending on the reagent and the solvent, 19 new sulfur containing compounds, including dithiones 4c and 4d, alpha,beta-unsaturated 3-thiones 3a-e, dimer-sulfides 2a-e, 1,2,4-trithiolanes 5a-e and phosphonotrithioates 6b-e were synthesized. All newly prepared compounds were characterized by IR, (1)H- and (13)C-NMR spectroscopy and elemental analysis.

Beckmann rearrangement of (Z)-cholest-4-en-6-one oxime (4) (prepared in 4 steps starting from cholest-5-en-3β-ol ο1)) with thionyl chloride in dioxane solution afforded an enamide-type lactam, i.e. 7-aza-B-homocholest-4-en-6-one (6) as a single product. Photoreaction of the same compound in methanol or benzene-acetic acid solution gave a mixture of products, with the formation of the parent ketone 3 and the occurrence of Z/E isomerization, while the lactam 6 was obtained only when the reaction was performed in methanol and then in very low yield (7%). Bekmanovo premeštanje (Z)-holest-4-en-6-on oksima (4) (koji je dobijen u 4 faze, polazeći od holest-5-en-3 β-ola (1)) sa tionil-hloridom u dioksanskom rastvoru, kao jedini proizvod daje laktam enamidnog tipa, tj. 7-aza-B-homoholest-4-en-6-on (6). Fotoreakcijom istog jedinjenja u metanolu ili u rastvoru benzen-sirćetna kiselina, nastaje smesa proizvoda koju čine polazni keton 3 i proizvodi Z/E izomerizacije, dok je laktam 6 dobiven u vrlo niskom prinosu (7%) samo u metanolnom rastvoru.

The acid-catalyzed reaction of (Z)- and (E)-B-nor-5,10-seco-ketones 2 and 3 resulted in an intramolecular cyclization to give the 5-hydroxy-A-nor-1β,5β-10(19)-methylidene derivative 8, the 5β-hydroxy-A-nor-1(10)-unsaturated compound 9 and the 5β,10β-dihydroxy A-nor-product 10, from the (Z)-isomer and the 5-hydroxy-A-nor-1β,5β-10(19)-methylidene product 11, from the (E)-isomer. Upon UV-irradiation, the (Z)- and (E)-seco-ketones 2 and 3 underwent a reversible (Z)/(E) and (E)/(Z)-isomerization and in addition to a transannular photocyclization to afford the 10(19)-methylidene derivatives 8 and 11, respectively, while photolysis of the 10(19)-methylidene-B-nor-5,10-seco-ketone 4 gave the oxetane derivative 12. Kiselo-katalizovana reakcija (Z)- i (E)-B-nor-5,10-seko-ketona 2 i 3 rezultuje u intramolekulskoj ciklizaciji dajući 5-hidroksi-A-nor-1β,5β-10(19)-metilidenski derivat 8, 5β-hidroksi A-nor-1(10)-nezasićeno jedinjenje 9 i 5β,10β-dihidroksi-A-nor-proizvod 10, iz Z-izomera, i 5-hidroksi-A-nor-1β,5β-10(19)-metilidenski proizvod 11, iz E-izomera. (Z)- i (E)-Seko- ketoni 2 i 3 UV-ozračivanjem podležu reverzibilnoj (Z)/(E) odnosno (E)/(Z) izomerizaciji, kao i transanularnoj fotociklizaciji dajući 10(19)-metilidenske derivate 8 odnosno 11, dok se fotolizom 10(19)-metilidenskog-5,10-seko-ketona 4 gradi oksetanski derivat 12.

A simple one-put procedure for the synthesis of the 5,6-seco-steroidal acids 9a,b in described in this paper. It consists of the epoxidation of the ▲ 5 -steroids, i.e., cholesteryl acetate (8a) and 17-oxo-aandrost-5-en-3β-yl acetate (8b) with peracetic acid (generated in situ by the H 2 WO 4 H 2 O 2 system), followed by the CrO 3 /H 2 SO_ oxidation of the thus formed epoxides. The 5,6-seco-steroidal acids 9a,b (obtained in about 90% and 77% yield, respectively) are transformed to the corresponding B-norsteroids by the known method (Beayer-Villiger oxidation and subsequent thermolysis of the respective β-lactones).

5-Hydroxy-5α-cholest-8-en-3β-yl acetate (8) (prepared in 6 steps starting from 7-dehydrocholesteryl acetate (1) was transformed with ruthenium tetroxide to 5-hydroxy-8,9-dioxo-8,9-seco-5α-cholestan-3β-yl acetate (9). Treatment of the latter 8,9-seco-5-hydroxy derivative with lead tetraacetate (LTA) or mercuric oxide/iodine reagent (HgO/I2) resulted, instead of the expected oxidative β-fragmentation of its C(5)-C(10) bond, in the competing non-regio and non-stereoselective acetoxylation of the α-positions next to the 8- and 9-oxo functions (with LTA), and in the ≈ 82% recovery of the starting material (with HgO/I2). The results are discussed in terms of the strong hydrogen bonding which exists between the 5α-hydroxyl and the 8-oxo group.

In this paper is described a synthetic pathway to the modified 5, 10:8, 14-bisfragmentation cholestene derivatives 10, 11 and 12, which involves introduction of the Δ8(14)-double bond and 5α-hydroxyl group in the cholestane molecule and subsequent cleavage of the olefinic C(8)-C(14) bond (with ruthenium tetroxide) and C(5)-C(10) bond (with mercuric oxide/iodine or lead tetracetate/iodine).

The reactivity of the butoxy and 3-methylcyclohexyl radicals, as representatives of alkoxy radicals, was studied by MNDO-PM3 semiempirical MO method. In both cases it was found that the oxy radical underwent easily 1,5-H migration giving a δ-hydroxyalkyl radical. The hydrogen abstraction reaction goes through two transition states. The first transition state (TS) with short O-H distance has an energy very similar to, or lower than, the TS for 1,5-H migration. The second TS is of higher energy and is much product-like. The overall cyclisation reaction has a high activation energy (over 40 kcal mol-1), and is therefore unlikely to occur spontaneously. Most likely, the cyclisation step needs assistance of some other surrounding molecules to speed up the reaction.

Kinetic measurements of the solvolysis of (Z)-3α- and (Z)-3β-, and (E)-3α- and (E)-3β-tosyloxy-5,10-secocholest-1(10)-en-5-ones in buffered aqueous acetone (90 : 10 v/v) reveal that the (Z)-3α-, (E)-3α-, and (E)-3β-tosylates are solvolysed according to a first-order rate law (the relative rates being ca. 1 : 3 : 8), while the (Z)-3β-ester, under the same conditions, reacts at a much slower rate by a complex mechanism, the kinetics of which are best approximated by a second-order law. These data and product analysis indicate that the former three esters are solvolysed with considerable double bond participation [resulting in the case of the (E)-3-esters in intramolecular cyclopropane ring closure], and that this interaction is unimportant for the (Z)-3β-tosylate. On the basis of conformational analysis of the starting tosylates and stereoelectronic requirements for homoallylic interaction, a possible mechanistic pathway for these solvolyses is proposed.